Dr. Harleen Francis Quinzel, also known as Harley Quinn, first appeared in the Batman: The Animated Series episode "Jokers Favor" (episode #022, original air date: September 11, 1992) where she served as a humorous female sidekick to the Joker. In her first appearances she was depicted as a character completely devoted to the Joker, totally oblivious to his psychotic nature and his obvious lack of affection for her - a characterization that has remained more or less consistent throughout her subsequent appearances. Her name is a play on the word 'harlequin'.

The origin of the character was recounted in a 1994 graphic novel The Batman Adventures: Mad Love. Told in the style and continuity of Batman: The Animated Series and written and drawn by Paul Dini and Bruce Timm (two of the producers of the animated series and Harley's creators) the comic book revealed Harley's origins as an Arkham Asylum psychiatrist who fell in love with the Joker. The story was widely praised and won the Eisner and Harvey Awards for Best Single Issue Comic of the Year.

The Mad Love story was originally thought too violent for the animated series, though it was eventually adapted in The New Batman Adventures series episode "Mad Love" in 1999. This made it the first "animated style" comic book which was adapted for the series (the other being a holiday special adapted into the episode "Holiday Knights").

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Harleen Quinzel was a psychiatric intern at Arkham Asylum. Despite receiving high grades in college, she was not a particularly intellectual or strong-minded woman, having only gotten through college by seducing her professors. While researching the lunatics at Arkham, she became fascinated with one particular inmate. Ambitiously volunteering to analyze him, she fell in love nearly instantly with the Joker during their sessions. After helping him escape from the asylum more than once Harleen was suspected by the authorities, who revoked her license and placed her in her own cell. During an earthquake in Gotham City, she fled and became Harley Quinn, the sidekick to the Clown Prince of Crime himself, The Joker.

Quinn's relationship with the Joker could only be described as "abusive": he yells at her, beats her (usually within an inch of her life) and abandons her whenever she becomes inconvenient or annoying, but she always comes back for more, convinced that he truly loves her and that his violence is "just a joke." The Joker, an expert manipulator, always knows just when to turn on the charm when he once again needs her.

One time, the Joker grew tired of Quinn, and he sent her off on a rocket.
She crash landed in Robinson Park in the center of Gotham and was found by Poison Ivy. When Harley regains consciousness, Ivy initially plans to kill her. The prospect of her own death totally fails to move Harley, and Ivy is curious as to why. She convinces Harley to tell her story, and comes to feel a kinship with Harley. Considering her another castoff, Ivy offers to help Harley take her revenge on both Batman and the Joker. Ivy took her back to her lair in a toxic waste dump and nursed her back to health. This included injecting Harley with a serum that Ivy had developed which has given Harley that immunizes her to various assorted toxins and Ivy's own poisonous touch and also dramatically enhances Harley's strength and speed. Ivy intends this to give her new friend an edge on Batman and the Joker. Quinn and Ivy teamed up and conducted a number of successful capers. Hot-blooded Harley, however, is angrier at the Joker than at Batman, and even initially works with the Dark Knight to help bring down the Clown Prince of Crime.

While Batman eliminates the villain's muscle, Quinn chases the Joker up a damaged building, intending to send him falling to his death. Before she can do so, however, the Joker apologizes. Falling in love with him again, she forgives him on the spot, and serves as his lieutenant throughout the rest of No Man's Land, as well as the Emperor Joker storyline. After this, Ivy dissolved the partnership in disgust. Ivy remains, however, her usual first point of call when she and The Joker are going through a rough patch. Ivy adopted the role of older sister and teller of harsh truths to Quinn about her helpless infatuation with The Joker.

She frequently refers to the Joker as "Puddin" and "Mr. J." and she refers to Poison Ivy as "Red" (a reference to her red hair).

In the One Year Later storyline, Harley Quinn resurfaces as an inmate at Arkham Asylum, glimpsed briefly in Detective Comics #823.

Harley next appeared in Batman #663, in which she helps the Joker with a plan to kill all his former henchmen, unaware that the "punchline" to the scheme is her own death. Upon realizing this, she shoots him in the shoulder.

In Birds of Prey #105, Harley Quinn joins the Secret Six as the sixth member. In issue #108, upon hearing that Oracle has sent the Russian authorities footage of teammate Deadshot murdering the Six's employer as payback for double-crossing them, Harley asks, "Is it a bad time to say 'I quit'?"

Harley Quinn has joined forces with Poison Ivy and Catwoman in the recent title Gotham City Sirens. Having moved in with Poison Ivy at The Riddler's townhouse, she meets up with Catwoman who offers for the three of them to live and work together. Ivy resolves that she and Harley would provide Catwoman with "positive female reinforcement", and the three then agree to become a team. However, Harley and Ivy have one condition: they demand that Catwoman reveal to them the true identity of the original Batman. Suddenly, however, a new villain who tried to take down Selina Kyle named Boneblaster breaks into the apartment and the three of them have to move after they defeat him.

Later, after a chance encounter with who she thought was Bruce Wayne (but was really disguised Hush), the Joker attempts to kill Harley, apparently out of jealousy. Quinn is rescued by Ivy and Selina, and it is later revealed that her attacker wasn't the real Joker, but one of his old henchmen impersonating him.

During the Holidays, Harley travels to Bensonhurst, Brooklyn, where she visits her family. Her brother seems to be lazy and unwilling to work, causing Harley to fuss at him about the situation. Her mother also voices her disapproval for Harley's status as a wanted criminal, even though her daughter tries to say that she has changed her ways. The meeting leads to Harley going to visit her father in prison. She and her dad talk of why he is in jail once again, and he tries to tell her that he will also change his path if Harley has done so. They share a moment, but Harley realizes that her 'Pop' is trying to find out where she has stashed money away for him. As Harley goes to exit the building, a guard asks for a picture. She tries to refuse, but the guard claims that her father promised she would; And he had given him money for the photo: This angers Harley even further.

Quinn soon returns to Gotham City, not wanting to stay anywhere near her family. She then goes back to living with Catwoman and Poison Ivy in an abandoned animal kennel, which she warmly regards as her new home.

In the animated series Quinn often teamed up with Poison Ivy to take on Batman. Quinn's friendship with Ivy was also one of the few villainous team-ups in the animated series seemingly rooted in genuine friendship. When Ivy demanded during one episode that Quinn stand up for herself, Quinn said "I'm nobody's doormat—am I?" Ivy replied, "If you had a middle name, it would be 'Welcome'."

Her eventual fate is shown in the movie Batman Beyond: Return of the Joker. She disappeared, and was presumed dead, after falling into a deep crevasse during Batman's final showdown with the Joker; however, bottomless pits are a notoriously unreliable means of death in fiction. Indeed, a scene toward the end of the film reveals that she survived to start a family, with her granddaughters (Delia and Deidre Dennis) inheriting her devotion to the Joker and eventually joining the Jokerz Gang as Dee-Dee. This scene exists primarily because Harley is Paul Dini's admitted favorite character (not to mention being his main original addition to the Batman mythos), and he was unsettled by having to kill her off, so he snuck that scene into the script on his own. It survived thanks to Bruce Timm, who felt the lighter moment was a perfect relief after the intensity of the climax.

In 2002, a live-action television series called Birds of Prey, loosely based on the comic of the same name, included Harley Quinn as a psychotic psychiatrist and main villain. The character was portrayed by actress Mia Sara, who replaced Sherilyn Fenn (originator of the role in an unaired pilot episode). The show aired only 13 episodes. In this show, Harley is portrayed as an older, far more calculating and sinister character than her bubbly comic and cartoon personas. She also does not wear a costume, although she does wear an outfit that is reminiscent of her cartoon costume in the series finale, "Devil's Eyes". In that episode, she used experimental technology to transfer metahuman mind control powers to herself. It is unknown about this version's relationship with the Joker, although she does make reference to him as "Mr. J." on a few occasions, laments his loss as Gotham's crime boss and hints at a past relationship reminiscent to that of the animated series.

The character proved so popular that a version of her was eventually added to the more serious Batman comic book canon. She first appeared in Batman #570, "The Code" as part of the "No Man's Land" story. The comic-book version of Quinn, like the comic-book version of The Joker, is more dangerously psychotic and less humorously kooky than the animated-series version.

Lego has made a minifigure of Harley Quinn who looks very similar to her Batman: The Animated Series appearnce. She comes in the set with a large "truck" with a hammer on the side and a lego version of Batman, who appears to be wearing the same batsuit as he does in The Dark Knight. Lego Batman comes with a vehicle resembling the Batpod, though very movie unaccurate.

In the video game Batman: Arkham Asylum, Quinn is a major antagonist, taking control of Arkham Asylum's security systems, freeing the Joker, and tracking Batman. She also traps several asylum staff members, forcing Batman to save them, and is still hopelessly in love with Joker. She also activates a pacification system which electrifies the floors of maximum security cell blocks, electrocuting a security guard and forcing Batman to flee into the waiting fists of her henchmen atop a control platform. In the end, Batman tracks Quinn's trail of destruction to an Extreme Incarceration area, where she and the Joker's thugs have overpowered the guards and seized control. Harley unleashes wave after wave of loosed inmates on the Dark Knight while turning on the electrified floors in an attempt to kill him. However, Batman defeats her and locks her up in a cell, where she continues to believe that 'Mr. J's just jokin' and that 'He'll save me, you'll see'.

After order was restored to the asylum upon the Joker's defeat, Quinn was released into the custody of the police as they took back Arkham by storm. A year and a half later, in Batman: Arkham Asylum's sequel, Gotham's new mayor, Quincy Sharp, declares Arkham unfit to house patients and has Quinn thrown into 'Arkham City', a sealed-off section of Gotham City where all criminals are taken to fight out an existence among themselves. Quinn dons a new costume and leads the Joker's gang in Arkham City, where anarchy reigns and the inmates are given only one rule: 'Do not Escape', as ruthlessly enforced by members of a private military firm assigned to police the perimeter. She is still portrayed as being in love with the Joker, despite the fact he is now infected by a potentially fatal disease.